Very early hypothermia induction in patients with severe brain injury (the National Acute Brain Injury Study: Hypothermia II): a randomised trial

Abstract

Summary Background The inconsistent effect of hypothermia treatment on severe brain injury in previous trials might be because hypothermia was induced too late after injury. We aimed to assess whether very early induction of hypothermia improves outcome in patients with severe brain injury. Methods The National Acute Brain Injury Study: Hypothermia II (NABIS: H II) was a randomised, multicentre clinical trial of patients with severe brain injury who were enrolled within 2·5 h of injury at six sites in the USA and Canada. Patients with non-penetrating brain injury who were 16–45 years old and were not responsive to instructions were randomly assigned (1:1) by a random number generator to hypothermia or normothermia. Patients randomly assigned to hypothermia were cooled to 35°C until their trauma assessment was completed. Patients who had none of a second set of exclusion criteria were either cooled to 33°C for 48 h and then gradually rewarmed or treated at normothermia, depending upon their initial treatment assignment. Investigators who assessed the outcome measures were masked to treatment allocation. The primary outcome was the Glasgow outcome scale score at 6 months. Analysis was by modified intention to treat. This trial is registered with ClinicalTrials.gov, NCT00178711. Findings Enrolment occurred from December, 2005, to June, 2009, when the trial was terminated for futility. Follow-up was from June, 2006, to December, 2009. 232 patients were initially randomised a mean of 1·6 h (SD 0·5) after injury: 119 to hypothermia and 113 to normothermia. 97 patients (52 in the hypothermia group and 45 in the normothermia group) did not meet any of the second set of exclusion criteria. The mean time to 35°C for the 52 patients in the hypothermia group was 2·6 h (SD 1·2) and to 33°C was 4·4 h (1·5). Outcome was poor (severe disability, vegetative state, or death) in 31 of 52 patients in the hypothermia group and 25 of 56 in the normothermia group (relative risk [RR] 1·08, 95% CI 0·76–1·53; p=0·67). 12 patients in the hypothermia group died compared with eight in the normothermia group (RR 1·30, 95% CI 0·58–2·52; p=0·52). Interpretation This trial did not confirm the utility of hypothermia as a primary neuroprotective strategy in patients with severe traumatic brain injury. Funding National Institute of Neurological Disorders and Stroke.

Declining mortality in neurocritical care patients: a cohort study in Southern Alberta over eleven years

“…Some practices, such as the use of hypothermia in TBI patients, decompressive craniectomy, and ICP monitoring, have been reported to lack efficacy at improving outcomes in preliminary clinical trials. [44][45][46] Nevertheless, our findings are in agreement with multiple observational studies suggesting that the development of specialized neurocritical care unitsusually supported by the presence of neurointensivists and utilizing evidence-based protocols-may contribute to improved patient outcomes. 28 International studies involving neurocritical care patients have suggested that there is considerable variability in outcomes between countries and individual centers.…”

Therapeutic Hypothermia for Acute Neurological Injuries

“…One might argue that a delayed initiation of hypothermia after injury might be contributory to the negative findings. However, as has been shown most recently, even the application of very early hypothermia after severe TBI (within 2.5 h after injury) did not confirm the usefulness of hypothermia as a primary neuroprotective treatment [109].…”

Perioperative temperature measurement and management: moving beyond the Surgical Care Improvement Project

“…The review found that the greatest benefit occurred when hypothermia was maintained for 48 hours; however hypothermia doubled the risk of pneumonia [60]. In 2011 the National Acute Brain Injury Study: Hypothermia II was published after being terminated early for futility [61]. No benefit could be attributed to early induced hypothermia in trauma patients [61].…”

“…In 2011 the National Acute Brain Injury Study: Hypothermia II was published after being terminated early for futility [61]. No benefit could be attributed to early induced hypothermia in trauma patients [61]. However, the group containing intentionally hypothermic patients had a higher daily 20,36 Possible hemodilution 83 Possible coagulation derangements 83 …”